This study attempts to investigate how future sea surface temperature increases will affect the size (radius of gale-force 17 m s−1 wind at 10 m height; i.e., R17) evolution of tropical cyclones that ...undergo extratropical transition (ET) through sensitivity experiments of sea surface temperature (SST) for Typhoon Songda (2016) in the northwestern Pacific. Two numerical experiments were carried out, including a control simulation (control) and a sensitivity experiment (SST4.5) with SST increased by 4.5 degrees in the entire domain. The results showed that Songda tended to be stronger and larger with projected higher SSTs. Moreover, the momentum equation for tangential wind was utilized to study the mechanism of R17 evolution in different SST scenarios, in which the radial absolute vorticity flux term played a dominant role in generating a positive tendency of tangential wind. The results indicate that before ET, higher SSTs in the entire domain led to more active rainbands in both inner-core and outer-core regions. As a result, stronger secondary circulation and low-level inflow extended outward, and the absolute angular momentum (AAM) importing from the outer region increased, which led to a larger R17 in SST4.5. During the ET, the peripheral baroclinically driven frontal convection induced extensive boundary layer inflow, which accelerated the tangential flow in the outer frontal region through strong inward AAM transport. However, due to the lower latitude of the cyclone and the strong frontolysis at the outer side of the cold pool in SST4.5, the peripheral frontal convection reached the location of R17 later; thus, the increase in the cyclone size lagged behind that in the control.
Colorectal cancer (CRC) is the third most common cancer worldwide and is associated with a poor clinical outcome and survival. Therefore, the development of novel therapeutic agents for CRC is ...imperative. Atractylenolide I (AT-I) is a sesquiterpenoid lactone derivative of Rhizoma Atractylodis macrocephalae that exhibits diverse biological activities, including anti-cancer activities. However, the effects and potential mechanism of AT-I in CRC have yet to be fully elucidated. In this study, we aimed to examine the anti-cancer properties of AT-I and the associated functional mechanisms
and
. We found that AT-I treatment significantly suppressed the viability of CRC cell lines and inhibited colony formation, but to a lesser extent in NCM460 cells. Annexin V/PI staining showed that AT-I induced apoptosis in CRC cells, accompanied by increased caspase-3 and PARP-1 cleavage, enhanced expression of Bax, and reduced expression of Bcl-2. Furthermore, AT-I blocked cell glycolysis by inhibiting both glucose uptake and lactate production in CRC cells, and specifically downregulated the expression of the rate-limiting glycolytic enzyme HK2. In contrast, it had no discernable effects on the glycolytic enzymes PFK and PKM2. A mechanistic study revealed that AT-1 negatively regulates STAT3 phosphorylation through direct interaction with JAK2, thereby inhibiting its activation. Moreover, restoring the expression of STAT3 reversed the effect of AT-I on apoptosis and glycolysis in CRC cells.
results revealed that AT-I significantly suppressed tumor growth in HCT116-xenografted mice. Collectively, our findings indicate that the anti-cancer activity of AT-I in CRC is associated with the induction of apoptosis and suppression of glycolysis in CRC cells,
the disruption of JAK2/STAT3 signaling. Our preliminary experimental data indicate that AT-I may have applications as a promising candidate for the treatment of CRC.
d,l-Sulforaphane (SFN), a synthetic analogue of broccoli-derived isomer l-SFN, exerts cytotoxic effects on multiple tumor cell types through different mechanisms and is more potent than the l-isomer ...at inhibiting cancer growth. However, the means by which SFN impairs glioblastoma (GBM) cells remains poorly understood. In this study, we investigated the anti-cancer effect of SFN in GBM cells and determined the underlying molecular mechanisms. Cell viability assays, flow cytometry, immunofluorescence, and Western blot results revealed that SFN could induced apoptosis of GBM cells in a dose- and time-dependent manner, via up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2. Mechanistically, SFN treatment led to increase the intracellular reactive oxygen species (ROS) level in GBM cells. Meanwhile, SFN also suppressed both constitutive and IL-6-induced phosphorylation of STAT3, and the activation of upstream JAK2 and Src tyrosine kinases, dose- and time-dependently. Moreover, blockage of ROS production by using the ROS inhibitor
-acetyl-l-cysteine totally reversed SFN-mediated down-regulation of JAK2/Src-STAT3 signaling activation and the subsequent effects on apoptosis by blocking the induction of apoptosis-related genes in GBM cells. Taken together, our data suggests that SFN induces apoptosis in GBM cells via ROS-dependent inactivation of STAT3 phosphorylation. These findings motivate further evaluation of SFN as a cancer chemopreventive agent in GBM treatment.
Background Image-based screening improves the detection of early-stage lung adenocarcinoma (LUAD)but also highlights the issue of high false-positive diagnoses, which puts patients at a risk of ...unnecessary over-treatment. Therefore, more precise discrimination criteria are required to ensure that patients with early-stage LUAD receive appropriate treatments. Methods We integrated 158 early-stage LUAD cases from 2 independent cohorts, including 30 matched resected specimens with complete radiological and pathological information, and 128 retrospective pathological pair-samples with partial follow-up data. This integration allowed us to conduct a correlation analysis between clinical phenotype and transcriptome landscape. Immunohistochemistry was performed using tissue microarrays to examine the expression of phospholipid phosphatase 2 (PLPP2) and lipid-raft markers. Lipidomics analysis was used to determine the changes of lipid components in PLPP2-overexpressed cells. To assess the effects of PLPP2 on the malignant phenotypes of LUAD cells, we conducted mice tumor-bearing experiments and in vitro cellular experiments by knocking down PLPP2 and inhibiting lipid raft synthesis with MbetaCD, respectively. Results Bioinformatics analysis indicated that the co-occurrence of lipid raft formation and rapid cell proliferation might exhibit synergistic effects in driving oncogenesis from lung preneoplasia to adenocarcinoma. The enhanced activation of the cell cycle promoted the transition from non-invasive to invasive status in early-stage LUAD, which was related to an increase in lipid rafts within LUAD cells. PLPP2 participated in lipid raft formation by altering the component contents of lipid rafts, such as esters, sphingomyelin, and sphingosine. Furthermore, elevated PLPP2 levels were identified as an independent prognostic risk factor for LUAD patients. Further results from in vivo and in vitro experiments confirmed that PLPP2 could induce excessive cell proliferation by enhancing lipid raft formation in LUAD cells. Conclusions Our study has revealed the characteristics of gene expression profiles in early-stage LUAD patients with the different radiological and pathological subtypes, as well as deciphered transcriptomic evolution trajectory from preneoplasia to invasive LUAD. Furthermore, it suggests that PLPP2-mediated lipid raft synthesis may be a significant biological event in the initiation of early-stage LUAD, offering a potential target for more precise diagnosis and therapy in clinical settings. Keywords: Early stage lung adenocarcinoma, Transcriptome sequencing, Lipid rafts, Phospholipid phosphatase 2, Cell proliferation
Small-cell lung cancer (SCLC) is characterized as an aggressive tumor with brain metastasis. Although preventing SCLC metastasis to the brain is immensely important for survival, the molecular ...mechanisms of SCLC cells penetrating the blood-brain barrier (BBB) are largely unknown. Recently, visfatin has been considered as a novel pro-inflammatory adipocytokine involved in various cancers. Herein, we present evidence that elevated levels of visfatin in the serum of SCLC patients were associated with brain metastasis, and visfain was increased in NCI-H446 cells, a SCLC cell line, during interacting with human brain microvascular endothelial cells (HBMEC). Using in vitro BBB model, we found that visfatin could promote NCI-H446 cells migration across HBMEC monolayer, while the effect was inhibited by knockdown of visfatin. Furthermore, our findings indicated that CC chemokine ligand 2 (CCL2) was involved in visfatin-mediated NCI-H446 cells transendothelial migtation. Results also showed that the upregulation of CCL2 in the co-culture system was reversed by blockade of visfatin. In particular, visfatin-induced CCL2 was attenuated by specific inhibitor of PI3K/Akt signaling in NCI-H446 cells. Taken together, we demonstrated that visfatin was a prospective target for SCLC metastasis to brain, and understanding the molecular mediators would lead to effective strategies for inhibition of SCLC brain metastasis.
Chirality‐based semiconducting nanocrystals, as an emerging area, are envisioned to have great potential in chiral sensing, biomedicine, and chiroptical devices. Herein, chiral substoichiometric ...molybdenum oxide (l/d‐Cys‐MoO3−x) nanoparticles are synthesized via step‐by‐step reduction treatment with chiral cysteine molecules. The obtained nanoparticles are used as visible‐ and near‐infrared‐light dual responsive photothermal therapy agent for tumor cell ablation. Notably, the chiral nanoparticles show chiral selectivity for incident light, i.e., when irradiated by left‐circularly polarized light, l‐Cys‐MoO3−x is the most sensitive agent giving the highest mortality for HeLa cell ablation in vitro, and vice versa for right‐circularly polarized light with d‐Cys‐MoO3−x. In comparison to traditional photothermal therapy with near‐field light source, the investigations with chiral visible light at 532 nm indicate the possibility of chiral Cys‐MoO3−x nanoparticles for visible light‐based phototherapy via metal–ligand charge transfer chirality, which provides insights for new methods in nanotechnology supported photothermal treatments.
Visible‐ and near‐infrared (NIR)‐light responsive chiral substoichiometric MoO3−x nanocrystals are investigated and applied as an ultrasensitive photothermal therapy agent for tumor cell ablation. Compared to traditional photothermal therapy, such chiral MoO3−x nanocrystal‐based systems show chiral selectivity for incident circular polarized light, resulting in enhanced photothermal therapy performance with both visible and NIR polarized light sources.
Nucleotide‐binding and oligomerization domain‐containing protein 2 (NOD2) was a member of the NOD‐like receptor family and played an important role in the innate immune response. Dysregulated NOD2 ...had been reported to contribute to tumorigenesis and progression. Here, we investigated that decreased NOD2 expressions could affect the phenotypic polarization of tumour‐associated macrophages and thus lead to the poor prognosis of lung adenocarcinoma patients. We clustered the patients by the single‐sample gene set enrichment analysis of tumour microenvironment and 13 prognostic differentially expressed immune‐related genes (PDEIRGs) were obtained based on prognostic analyses. After multiple assessments on the 13 PDEIRGs, NOD2 was considered to be the central immune gene and had a strong effect on suppressing tumour progression. Decreased NOD2 expression could be induced by cancer cells and lead to the phenotypic polarization of macrophages from protective M1 phenotype to pro‐tumorigenic M2 subtype which might be attributed to the down‐regulating of NF‐κB signalling pathway. This study draw attention to the role of inhibited innate immune function mediated by depletion of NOD2 in the TME. Our work also points to a potential strategy of NOD2‐mediated TAM‐targeted immunotherapy.
Abstract
Chirality‐based semiconducting nanocrystals, as an emerging area, are envisioned to have great potential in chiral sensing, biomedicine, and chiroptical devices. Herein, chiral ...substoichiometric molybdenum oxide (
l
/
d
‐Cys‐MoO
3−
x
) nanoparticles are synthesized via step‐by‐step reduction treatment with chiral cysteine molecules. The obtained nanoparticles are used as visible‐ and near‐infrared‐light dual responsive photothermal therapy agent for tumor cell ablation. Notably, the chiral nanoparticles show chiral selectivity for incident light, i.e., when irradiated by left‐circularly polarized light,
l
‐Cys‐MoO
3−
x
is the most sensitive agent giving the highest mortality for HeLa cell ablation in vitro, and vice versa for right‐circularly polarized light with
d
‐Cys‐MoO
3−
x
. In comparison to traditional photothermal therapy with near‐field light source, the investigations with chiral visible light at 532 nm indicate the possibility of chiral Cys‐MoO
3−
x
nanoparticles for visible light‐based phototherapy via metal–ligand charge transfer chirality, which provides insights for new methods in nanotechnology supported photothermal treatments.
Colorectal cancer (CRC) is a common form of cancer associated with a high mortality rate and poor prognosis. Given the limited efficacy of current therapies for CRC, interest in novel therapeutic ...agents isolated from natural sources has increased. We studied the anticancer properties of isobavachalcone (IBC), a flavonoid isolated from the herb
, which is used in traditional Chinese medicine, in an in vitro model of CRC.
Cell viability and growth of CRC cells were determined by Cell Counting Kit-8 and colony formation assays following treatment with varying concentrations of IBC, respectively. Apoptosis was examined by 4',6-diamidino-2-phenylindole staining and flow cytometry with Annexin V/propidium iodide double staining. Western blot analysis was used to analyze expression of apoptosis-associated protein pathway and the AKT/GSK-3β/β-catenin signaling pathway.
Initial experiments showed that IBC inhibited proliferation and colony formation of human CRC cell lines in dose- and time-dependent manners. The antiproliferative effect of IBC resulted from induction of apoptosis, as evidenced by morphological changes in the nucleus, flow cytometry analysis, upregulation of cleaved caspase-3 and cleaved PARP, changes in the ratio of the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax, translocation of Bax from the cytosol to the mitochondria, and decreased expression of two inhibitors of apoptosis family proteins, XIAP, and survivin. Western blot analysis of signaling pathway proteins demonstrated that IBC downregulated Wnt/β-catenin signaling, which has previously been associated with CRC, by inhibiting the AKT/GSK-3β signaling pathway.
This study demonstrated that IBC inhibited cell proliferation and induced apoptosis through inhibition of the AKT/GSK-3β/β-catenin pathway in CRC. These results suggest the potential of IBC as a novel therapeutic agent for the treatment of CRC.
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